Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New Paths Explored for Curbing Genetic Malfunctions

17.01.2013
Investigators probe mechanisms of RNA synthesis

One of the most extraordinary properties of living cells is their ability to precisely reproduce themselves through processes that transfer genetic information from one cell to the next.

However, there are times when one of the steps of information transfer, transcription, goes awry at the cellular level, potentially producing diseases such as cancer and other health disorders. Unraveling how those processes work and how substandard transcription can be prevented is a major goal of biomedical science. Progress in this area may also lead the way toward development of drugs that target the genetic transcription process in disease-causing microbes.

A research team led by Arkady Mustaev, PhD, of the Public Health Research Institute (PHRI) at the University of Medicine and Dentistry of New Jersey-New Jersey Medical School, has published a study posted online by the Journal of Biological Chemistry, that describes an effort by the investigators to understand the underlying mechanisms of high precision (fidelity) of RNA synthesis by RNA polymerase, the major enzyme that promotes the transcription process. They attempted to influence the role of active center tuning (ACT) -- a mechanism they first identified -- in the process of transcription fidelity, which is the accurate copying of genetic information.

ACT is a rearrangement of the RNA polymerase catalytic center from an inactive to a catalytically proficient state. The investigators found that both reactions of NTP polymerization and hydrolytic RNA proofreading are performed by the same active center that includes two magnesium (Mg) ions coordinated by aspartate triad. The active center is normally “turned off” since it is missing one of Mg ions. Correct NTP substrates as well as misincorporated RNA residues can promote ACT by inclusion of the missing Mg ion through establishing recognition contacts in the active center. Incorrect substrates cannot trigger ACT and are rejected. The investigators also demonstrate that transcript cleavage factors Gre build on ACT mechanism by providing the residues for stabilization of catalytic Mg ion and for activation of the attacking water causing 3000-4000-fold reaction enhancement thereby strongly reinforcing proofreading.

The suggested ACT mechanism is fundamentally different from that proposed for DNA replication enzyme, DNA polymerase (DNAP) in which the active centers for DNA synthesis and proofreading are separated and discrimination between deoxy- and ribo-substrate is achieved through strict fitting requirements for the sugar rather than through active center rearrangement. In DNAP active center carboxylates stem from rigid scaffolds, while in multisubunit RNAP they reside in an apparently flexible loop. ACT is accompanied by significant re-shaping of the loop, which would not be possible in DNAP.

This study was supported by NIH grant RO1 GM-30717-21.

Journalists who wish to speak with Dr. Arkady Mustaev should contact Rob Forman, UMDNJ Chief of News Services, at 973-972-7276 or formanra@umdnj.edu .

About PHRI:
The Public Health Research Institute (PHRI) (www.phri.org) is a 71-year-old biomedical research organization that emphasizes translational approaches to overcome critical issues of infectious diseases. Founded in New York City, PHRI became an academic affiliate of the New Jersey Medical School-University of Medicine and Dentistry of New Jersey (UMDNJ) in 2006. PHRI’s 23 laboratories work on a wide range of infectious diseases issues including HIV and other viruses, TB, hospital and community acquired bacterial infections, fungal infections, biodefense and drug resistance. Fundamental knowledge of the disease process and its components is used to develop a new generation of diagnostics, therapeutics and vaccines. For more than 7 decades, PHRI’s culture of research innovation and excellence has led to important new discoveries in science and medicine.
About UMDNJ:
The University of Medicine and Dentistry of New Jersey (UMDNJ) is New Jersey’s only health sciences university with more than 6,000 students on five campuses attending three medical schools, the State’s only dental school, a graduate school of biomedical sciences, a school of health related professions, a school of nursing and New Jersey’s only school of public health. UMDNJ operates University Hospital, a Level I Trauma Center in Newark, and University Behavioral HealthCare, which provides a continuum of healthcare services with multiple locations throughout the State.

Rob Forman | Newswise
Further information:
http://www.umdnj.edu

More articles from Life Sciences:

nachricht Pathogenic bacteria hitchhiking to North and Baltic Seas?
22.07.2016 | Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung

nachricht Unconventional quasiparticles predicted in conventional crystals
22.07.2016 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Mapping electromagnetic waveforms

Munich Physicists have developed a novel electron microscope that can visualize electromagnetic fields oscillating at frequencies of billions of cycles per second.

Temporally varying electromagnetic fields are the driving force behind the whole of electronics. Their polarities can change at mind-bogglingly fast rates, and...

Im Focus: Continental tug-of-war - until the rope snaps

Breakup of continents with two speed: Continents initially stretch very slowly along the future splitting zone, but then move apart very quickly before the onset of rupture. The final speed can be up to 20 times faster than in the first, slow extension phase.phases

Present-day continents were shaped hundreds of millions of years ago as the supercontinent Pangaea broke apart. Derived from Pangaea’s main fragments Gondwana...

Im Focus: A Peek into the “Birthing Room” of Ribosomes

Scaffolding and specialised workers help with the delivery – Heidelberg biochemists gain new insights into biogenesis

A type of scaffolding on which specialised workers ply their trade helps in the manufacturing process of the two subunits from which the ribosome – the protein...

Im Focus: New protocol enables analysis of metabolic products from fixed tissues

Scientists at the Helmholtz Zentrum München have developed a new mass spectrometry imaging method which, for the first time, makes it possible to analyze hundreds of metabolites in fixed tissue samples. Their findings, published in the journal Nature Protocols, explain the new access to metabolic information, which will offer previously unexploited potential for tissue-based research and molecular diagnostics.

In biomedical research, working with tissue samples is indispensable because it permits insights into the biological reality of patients, for example, in...

Im Focus: Computer Simulation Renders Transient Chemical Structures Visible

Chemists at the University of Basel have succeeded in using computer simulations to elucidate transient structures in proteins. In the journal Angewandte Chemie, the researchers set out how computer simulations of details at the atomic level can be used to understand proteins’ modes of action.

Using computational chemistry, it is possible to characterize the motion of individual atoms of a molecule. Today, the latest simulation techniques allow...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

GROWING IN CITIES - Interdisciplinary Perspectives on Urban Gardening

15.07.2016 | Event News

SIGGRAPH2016 Computer Graphics Interactive Techniques, 24-28 July, Anaheim, California

15.07.2016 | Event News

Partner countries of FAIR accelerator meet in Darmstadt and approve developments

11.07.2016 | Event News

 
Latest News

Hey robot, shimmy like a centipede

22.07.2016 | Information Technology

New record in materials research: 1 terapascals in a laboratory

22.07.2016 | Physics and Astronomy

University of Graz researchers challenge 140-year-old paradigm of lichen symbiosis

22.07.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>